7-[D(-)-.alpha.-amino-.alpha.-(p-hydroxyphenyl)acetamido]-3-(1,2,3-triazol- 4(5)-yl-thiomethyl)-3-cephem-4-carboxylic acid is a synthetic cefalosporin, active by the oral route, to which the International Non-Proprietary Name (INN) "cefatrizine" has been given. Cefatrizine, represented by the formula: ##STR1## has the drawback of being poorly stable and requires careful handling in its preparation and of the pharmaceutical formulations containing it.
German Patent Application DE No. 2,500,386 discloses the adduct of cefatrizine with 1,2-propylene glycol, hereinafter called "cefatrizine propylene glycolate", and represented by the formula: ##STR2## This derivative solves the problems related to the instability of cefatrizine and, moreover, exhibits improved pharmacological kinetics with respect to cefatrizine.
According to the above-identified application, cefatrizine propylene glycolate is prepared directly from cefatrizine, or from its methanolate, by reaction with 1,2-propylene glycol. Cefatrizine is first synthesized by reaction of 7-amino-3-(1,2,3-triazol-4(5)-yl)thiomethyl-3-cephem-4-carboxylic acid having the formula: ##STR3## with a reactive derivative of D(-)-p-hydroxyphenylglycine. Compound (B) was silylated prior to reaction, as described in the German Patent Application No. 2,364,192.
In the industrial preparation of cefatrizine propylene glycolate a double solvatation is carried out: first with methanol and then with 1,2-propylene glycol. When using this method, the pH must be adjusted, up to a value of about 4, before isolation of product.